tbuckley/cabot-search huggingface dataset:
Fused Cytomembrane‐Camouflaged Nanoparticles for Tumor‐Specific Immunotherapy
Authors: Ping Ji, Xin‐Chen Deng, Xiao‐Kang Jin, Shi‐Man Zhang, Jia‐Wei Wang, Jun Feng, Wei‐Hai Chen, Xian‐Zheng Zhang
Journal: Advanced Healthcare Materials (2023)

Abstract Tumor immunotherapy is commonly hindered by inefficient delivery and presentation of tumor antigens as well as immunosuppressive tumor microenvironment. To overcome these barriers, a tumor‐specific nanovaccine capable of delivering tumor antigens and adjuvants to antigen‐presenting cells and modulating the immune microenvironment to elicit strong antitumor immunity is reported. This nanovaccine, named FCM@4RM, is designed by coating the nanocore (FCM) with a bioreconstituted cytomembrane (4RM). The 4RM, which is derived from fused cells of tumorous 4T1 cells and RAW264.7 macrophages, enables effective antigen presentation and stimulation of effector T cells. FCM is self‐assembled from Fe(II), unmethylated cytosine‐phosphate‐guanine oligodeoxynucleotide (CpG), and metformin (MET). CpG, as the stimulator of toll‐like receptor 9, induces the production of pro‐inflammatory cytokine and the maturation of cytotoxic T lymphocytes (CTLs), thereby enhancing antitumor immunity. Meanwhile, MET functions as the programmed cell death ligand 1 inhibitor and can restore the immune responses of T cells against tumor cells. Therefore, FCM@4RM exhibits high targeting capabilities toward homologous tumors that develop from 4T1 cells. This work offers a paradigm for developing a nanovaccine that systematically regulates multiple immune‐related processes to achieve optimal antitumor immunotherapy.
Using Modern Modalities to Improve Population Health and Advance Food and Health Equity
Authors: Roopa Kalyanaraman Marcello
Journal: JAMA Pediatrics (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
A Comprehensive Multilevel Analysis of the Bucharest Early Intervention Project: Causal Effects on Recovery From Early Severe Deprivation
Authors: Lucy S. King, Katherine L. Guyon-Harris, Emilio A. Valadez, Anca Radulescu, Nathan A. Fox, Charles A. Nelson, Charles H. Zeanah, Kathryn L. Humphreys
Journal: American Journal of Psychiatry (2023)

Objective: The Bucharest Early Intervention Project is the first randomized controlled trial of foster care as an alternative to institutional care. The authors synthesized data from nearly 20 years of assessments of the trial to determine the overall intervention effect size across time points and developmental domains. The goal was to quantify the overall effect of the foster care intervention on children’s outcomes and examine sources of variation in this effect, including domain, age, and sex assigned at birth. Methods: An intent-to-treat approach was used to examine the causal effects of the randomized controlled trial for 136 children residing in institutions in Bucharest, Romania (baseline age, 6–31 months) who were randomly assigned to either foster care (N=68) or care as usual (N=68). At ages 30, 42, and 54 months and 8, 12, and 16–18 years, children were assessed for IQ, physical growth, brain electrical activity (EEG), and symptoms of five types of psychopathology. Results: Participants provided 7,088 observations across follow-up waves. Children assigned to foster care had better cognitive and physical outcomes and less severe psychopathology than did those who received care as usual. The magnitude of these effect sizes remained stable across development. The foster care intervention most influenced IQ and disorders of attachment/social relatedness. Conclusions: Young children benefit from placement in families after institutional care. The benefits of foster care for previously institutionalized children were remarkably stable across development.
Association of Prehospital Transfusion With Mortality in Pediatric Trauma
Authors: Katrina M. Morgan, Elissa Abou-Khalil, Stephen Strotmeyer, Ward M. Richardson, Barbara A. Gaines, Christine M. Leeper
Journal: JAMA Pediatrics (2023)

Importance Optimal hemostatic resuscitation in pediatric trauma is not well defined. Objective To assess the association of prehospital blood transfusion (PHT) with outcomes in injured children. Design, Setting, and Participants This retrospective cohort study of the Pennsylvania Trauma Systems Foundation database included children aged 0 to 17 years old who received a PHT or emergency department blood transfusion (EDT) from January 2009 and December 2019. Interfacility transfers and isolated burn mechanism were excluded. Analysis took place between November 2022 and January 2023. Exposure Receipt of a blood product transfusion in the prehospital setting compared with the emergency department. Main Outcomes and Measures The primary outcome was 24-hour mortality. A 3:1 propensity score match was developed balancing for age, injury mechanism, shock index, and prehospital Glasgow Comma Scale score. A mixed-effects logistic regression was performed in the matched cohort further accounting for patient sex, Injury Severity Score, insurance status, and potential center-level heterogeneity. Secondary outcomes included in-hospital mortality and complications. Results Of 559 children included, 70 (13%) received prehospital transfusions. In the unmatched cohort, the PHT and EDT groups had comparable age (median [IQR], 47 [9-16] vs 14 [9-17] years), sex (46 [66%] vs 337 [69%] were male), and insurance status (42 [60%] vs 245 [50%]). The PHT group had higher rates of shock (39 [55%] vs 204 [42%]) and blunt trauma mechanism (57 [81%] vs 277 [57%]) and lower median (IQR) Injury Severity Score (14 [5-29] vs 25 [16-36]). Propensity matching resulted in a weighted cohort of 207 children, including 68 of 70 recipients of PHT, and produced well-balanced groups. Both 24-hour (11 [16%] vs 38 [27%]) and in-hospital mortality (14 [21%] vs 44 [32%]) were lower in the PHT cohort compared with the EDT cohort, respectively; there was no difference in in-hospital complications. Mixed-effects logistic regression in the postmatched group adjusting for the confounders listed above found PHT was associated with a significant reduction in 24-hour (adjusted odds ratio, 0.46; 95% CI, 0.23-0.91) and in-hospital mortality (adjusted odds ratio, 0.51; 95% CI, 0.27-0.97) compared with EDT. The number needed to transfuse in the prehospital setting to save 1 child’s life was 5 (95% CI, 3-10). Conclusions and Relevance In this study, prehospital transfusion was associated with lower rates of mortality compared with transfusion on arrival to the emergency department, suggesting bleeding pediatric patients may benefit from early hemostatic resuscitation. Further prospective studies are warranted. Although the logistics of prehospital blood product programs are complex, strategies to shift hemostatic resuscitation toward the immediate postinjury period should be pursued.
Assessment of Screening Tools to Identify Substance Use Disorders Among Adolescents
Authors: Sharon Levy, Melissa Brogna, Machiko Minegishi, Geetha Subramaniam, Jennifer McCormack, Margaret Kline, Eleanor Menzin, Sophie Allende-Richter, Alyssa Fuller, Mitra Lewis, Julia Collins, Zach Hubbard, Shannon G. Mitchell, Roger Weiss, Elissa Weitzman
Journal: JAMA Network Open (2023)

Importance Efficient screening tools that effectively identify substance use disorders (SUDs) among youths are needed. Objective To evaluate the psychometric properties of 3 brief substance use screening tools (Screening to Brief Intervention [S2BI]; Brief Screener for Tobacco, Alcohol, and Drugs [BSTAD]; and Tobacco, Alcohol, Prescription Medication, and Other Substances [TAPS]) with adolescents aged 12 to 17 years. Design, Setting, and Participants This cross-sectional validation study was conducted from July 1, 2020, to February 28, 2022. Participants aged 12 to 17 years were recruited virtually and in person from 3 health care settings in Massachusetts: (1) an outpatient adolescent SUD treatment program at a pediatric hospital, (2) an adolescent medicine program at a community pediatric practice affiliated with an academic institution, and (3) 1 of 28 participating pediatric primary care practices. Participants were randomly assigned to complete 1 of the 3 electronic screening tools via self-administration, followed by a brief electronic assessment battery and a research assistant–administered diagnostic interview as the criterion standard measure for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition ( DSM-5 ) diagnoses of SUDs. Data were analyzed from May 31 to September 13, 2022. Main Outcomes and Measures The main outcome was a DSM-5 diagnosis of tobacco/nicotine, alcohol, or cannabis use disorder as determined by the criterion standard World Mental Health Composite International Diagnostic Interview Substance Abuse Module. Classification accuracy of the 3 substance use screening tools was assessed by examining the agreement between the criterion, using sensitivity and specificity, based on cut points for each tool for use disorder, chosen a priori from previous studies. Results This study included 798 adolescents, with a mean (SD) age of 14.6 (1.6) years. The majority of participants identified as female (415 [52.0%]) and were White (524 [65.7%]). High agreement between screening results and the criterion standard measure was observed, with area under the curve values ranging from 0.89 to 1 for nicotine, alcohol, and cannabis use disorders for each of the 3 screening tools. Conclusions and Relevance These findings suggest that screening tools that use questions on past-year frequency of use are effective for identifying adolescents with SUDs. Future work could examine whether these tools have differing properties when used with different groups of adolescents in different settings.
Segmental Uniparental Isodisomy Causing an “Inside-to-Outside” Limb-Girdle Muscular Dystrophy Due to a Homozygous Mutation in <i>POGLUT1</i>
Authors: Roula Ghaoui, Samuel Curtis, Karin S. Kassahn
Journal: JAMA Neurology (2023)

This case report describes segmental uniparental isodisomy causing an “inside-to-outside” limb-girdle muscular dystrophy due to a homozygous mutation in POGLUT1.
Age Dependency of Cardiovascular Outcomes With the Amyloidogenic <i>pV142I</i> Transthyretin Variant Among Black Individuals in the US
Authors: Senthil Selvaraj, Brian L. Claggett, C. Cristina Quarta, Bing Yu, Riccardo M. Inciardi, Joel N. Buxbaum, Thomas H. Mosley, Amil M. Shah, Sharmila Dorbala, Rodney H. Falk, Scott D. Solomon
Journal: JAMA Cardiology (2023)

Importance Hereditary transthyretin cardiac amyloidosis is an increasingly recognized cause of heart failure (HF) with distinct treatment. The amyloidogenic pV142I ( V122I) variant is present in 3% to 4% of Black individuals in the US and increases the risk for atrial fibrillation (AF), HF, and mortality. Since hereditary transthyretin cardiac amyloidosis demonstrates age-dependent anatomic penetrance, evaluation later in life may identify survivors at particularly high risk. Objective To estimate age-dependent risks for cardiovascular events with the variant. Design, Settings, and Participants This cohort study analyzed Black participants from the Atherosclerosis Risk in Communities (ARIC) study attending visit 1 (1987-1989) (followed up until 2019; median follow-up, 27.6 years). Data analyses were completed from June 2022 to April 2023. Exposure pV142I carrier status. Main outcomes The association between the variant and AF, HF hospitalization, mortality, and a composite of HF hospitalization or mortality was modeled by generating 10-year absolute risk differences for each year between ages 53 (the median age at visit 1) and 80 years, adjusting for the first 5 principal components of ancestry and sex. As an example, 5- and 10-year risk differences were specifically estimated for the composite outcome among participants surviving to age 80 years. Results Among 3856 Black participants (including 124 carriers) at visit 1, 2403 (62%) were women, 2140 (56%) had hypertension, and 740 (20%) had diabetes, with no differences between groups. The 10-year absolute risk difference between ages 53 and 80 years increased over time for each outcome. Statistical significance for increased 10-year risk difference emerged near ages 65 years for AF, 70 years for HF hospitalization, and 75 years for mortality. Among participants surviving to age 80 years, carriers had a 20% (95% CI, 2%-37%) and 24% (95% CI, 1%-47%) absolute increased risk for HF hospitalization or death at 5 and 10 years, respectively. Thus, at age 80 years, only 4 carriers would need to be identified to attribute 1 HF hospitalization or death over the following decade to the variant. Conclusions and Relevance In this study, age-specific risks were provided for relevant outcomes with the pV142I variant. Despite a relatively benign course during earlier years, Black individuals who carry the pV142I variant surviving into later life may be particularly vulnerable. These data may inform timing for screening, risk counseling to patients, and potential strategies for early targeted therapy.
Renal and blood pressure effects of dapagliflozin in recently hospitalized patients with heart failure with mildly reduced or preserved ejection fraction: Insights from the <scp>DELIVER</scp> trial
Authors: Safia Chatur, Jonathan W. Cunningham, Muthiah Vaduganathan, Finnian R. Mc Causland, Brian L. Claggett, Akshay S. Desai, Zi Michael Miao, Pardeep S. Jhund, Rudolf A. de Boer, Adrian F. Hernandez, Silvio E. Inzucchi, Mikhail N. Kosiborod, Carolyn S.P. Lam, Felipe A. Martinez, Sanjiv J. Shah, Magnus Petersson, Anna Maria Langkilde, John J.V. McMurray, Scott D. Solomon
Journal: European Journal of Heart Failure (2023)

Aims Patients recently hospitalized for heart failure (HF) often have unstable haemodynamics and experience worsening renal failure, and are at elevated risk for recurrent HF events. In DELIVER, dapagliflozin reduced HF events or cardiovascular death including among patients who were hospitalized or recently hospitalized. Methods and results We examined the effects of dapagliflozin versus placebo on estimated glomerular filtration rate (eGFR) slope (acute and chronic), 1‐month change in systolic blood pressure, and the occurrence of serious hypovolaemic or renal adverse events in patients with and without HF hospitalization within 30 days of randomization. The 654 (90 randomized during hospitalization, 147 1–7 days post‐discharge and 417 8–30 days post‐discharge) recently hospitalized patients had lower baseline eGFR compared with those without recent HF hospitalization (median [interquartile range] 55 [43, 71] vs. 60 [47, 75] ml/min/1.73 m 2 ). Dapagliflozin consistently reduced the risk of all‐cause ( p interaction = 0.20), cardiac‐related ( p interaction = 0.75), and HF‐specific ( p interaction = 0.90) hospitalizations, irrespective of recent HF hospitalization. In those recently hospitalized, acute placebo‐corrected eGFR reductions with dapagliflozin were modest and similar to patients without recent hospitalization (−2.0 [−4.1, +0.1] vs. −3.4 [−3.9, −2.9] ml/min/1.73 m 2 , p interaction = 0.12). Dapagliflozin's effect to slow chronic eGFR decline was similar regardless of recent hospitalization ( p interaction = 0.57). Dapagliflozin had a minimal effect on 1‐month systolic blood pressure and to a similar degree in patients with and without recent hospitalization (−1.3 vs.−1.8 mmHg, p interaction = 0.64). There was no treatment‐related excess in renal or hypovolaemic serious adverse events, irrespective of recent HF hospitalization. Conclusion In patients recently hospitalized with HF, initiation of dapagliflozin had minimal effects on blood pressure and did not increase renal or hypovolaemic serious adverse events, yet afforded long‐term cardiovascular and kidney protective effects. These data suggest that the benefit to risk ratio favours initiation of dapagliflozin among stabilized patients hospitalized or recently hospitalized for HF. Clinical Trial Registration: ClinicalTrials.gov NCT03619213.
Prevalence of Mental Health Diagnoses in Commercially Insured Children and Adolescents in the US Before and During the COVID-19 Pandemic
Authors: Loreen Straub, Brian T. Bateman, Seanna Vine, Krista F. Huybrechts
Journal: JAMA Network Open (2023)

This cross-sectional study examines trends in the prevalence of various mental health diagnoses in children and adolescents in the US, stratified by age and sex, before and during the COVID-19 pandemic.
Survival Trends in Children With Tetralogy of Fallot in Sweden From 1970 to 2017
Authors: Johanna Persson, Albert Gyllencreutz Castellheim, Mikael Dellborg, Kok Wai Giang, Christina Karazisi, Araz Rawshani, Zacharias Mandalenakis
Journal: JAMA Network Open (2023)

Importance Mortality in patients with tetralogy of Fallot (TOF) has decreased substantially since the start of surgical correction of this abnormality in the 1950s. However, nationwide data in Sweden comparing survival trends among pediatric patients with TOF with the general population are still limited. Objective To study survival trends in pediatric patients with TOF and compare them with matched controls. Design, Setting, and Participants A Swedish registry-based, nationwide, matched cohort study was conducted; data were collected from national health registers from January 1, 1970, to December 31, 2017. Patients with a registered diagnosis of TOF as well as controls without TOF matched by birth year and sex were included in the study. Follow-up data were collected from birth to age 18 years, death, or the end of follow-up (December 31, 2017), whichever occurred first. Data analysis was performed from September 10 to December 20, 2022. Survival trends among patients with TOF were compared with matched controls using Cox proportional hazards regression and Kaplan-Meier survival analyses. Main Outcomes and Measures All-cause mortality during childhood in patients with TOF and matched controls. Results The population included 1848 patients (1064 [57.6%] males; mean [SD] age, 12.4 [6.7] years) with TOF and 16 354 matched controls. The number of patients who underwent congenital cardiac surgery (henceforth, surgery group) was 1527 (897 [58.7%] males). In the whole TOF population from birth until age 18 years, 286 patients (15.5%) died during a mean (SD) follow-up time of 12.4 (6.7) years. In the surgery group, 154 of 1527 patients (10.1%) died during a follow-up time of 13.6 (5.7) years with a mortality risk of 21.9 (95% CI, 16.2-29.7) compared with matched controls. When stratified by birth period, a substantial decrease in the mortality risk was noted in the surgery group, from 40.6 (95% CI, 21.9-75.4) in those born in the 1970s to 11.1 (95% CI, 3.4-36.4) in those born in the 2010s. Survival increased from 68.5% to 96.0%. The risk of mortality for surgery decreased from 0.52 in the 1979s to 0.19 in the 2010s. Conclusions and Relevance The findings of this study suggest there has been substantial improvement in survival in children with TOF who underwent surgery from 1970 to 2017. However, the mortality rate is still significantly higher in this group compared with matched controls. Predictors of good and poor outcomes in this group need to be further explored, with the modifiable ones evaluated for further outcome improvements.
Cash Transfer Programs for Child Health—Elucidating Pathways and Optimizing Program Design
Authors: Erin F. Flynn, Chén C. Kenyon, Aditi Vasan
Journal: JAMA Pediatrics (2023)

This Viewpoint describes how nondirected cash transfer programs influence the dynamics of child poverty, highlights pathways by which poverty reduction programs could improve child health, and provides suggested directions for future research and policy.
Race and Ethnicity and Fracture Prediction Among Younger Postmenopausal Women in the Women’s Health Initiative Study
Authors: Carolyn J. Crandall, Joseph C. Larson, John T. Schousboe, JoAnn E. Manson, Nelson B. Watts, John A. Robbins, Peter Schnatz, Rami Nassir, Aladdin H. Shadyab, Karen C. Johnson, Jane A. Cauley, Kristine E. Ensrud
Journal: JAMA Internal Medicine (2023)

Importance The best approach to identify younger postmenopausal women for osteoporosis screening is uncertain. The Fracture Risk Assessment Tool (FRAX), which includes self-identified racial and ethnic information, and the Osteoporosis Self-assessment Tool (OST), which does not, are risk assessment tools recommended by US Preventive Services Task Force guidelines to identify candidates for bone mineral density (BMD) testing in this age group. Objective To compare the ability of FRAX vs OST to discriminate between younger postmenopausal women who do and do not experience incident fracture during a 10-year follow-up in the 4 racial and ethnic groups specified by FRAX. Design, Setting, and Participants This cohort study of Women’s Health Initiative participants included 67 169 women (baseline age range, 50-64 years) with 10 years of follow-up for major osteoporotic fracture (MOF; including hip, clinical spine, forearm, and shoulder fracture) at 40 US clinical centers. Data were collected from October 1993 to December 2008 and analyzed between May 11, 2022, and February 23, 2023. Main Outcomes and Measures Incident MOF and BMD (in a subset of 4607 women) were assessed. The area under the receiver operating characteristic curve (AUC) for FRAX (without BMD information) and OST was calculated within each racial and ethnic category. Results Among the 67 169 participants, mean (SD) age at baseline was 57.8 (4.1) years. A total of 1486 (2.2%) self-identified as Asian, 5927 (8.8%) as Black, 2545 (3.8%) as Hispanic, and 57 211 (85.2%) as White. During follow-up, 5594 women experienced MOF. For discrimination of MOF, AUC values for FRAX were 0.65 (95% CI, 0.58-0.71) for Asian, 0.55 (95% CI, 0.52-0.59) for Black, 0.61 (95% CI, 0.56-0.65) for Hispanic, and 0.59 (95% CI, 0.58-0.59) for White women. The AUC values for OST were 0.62 (95% CI, 0.56-0.69) for Asian, 0.53 (95% CI, 0.50-0.57) for Black, 0.58 (95% CI, 0.54-0.62) for Hispanic, and 0.55 (95% CI, 0.54-0.56) for White women. For discrimination of femoral neck osteoporosis, AUC values were excellent for OST (range, 0.79 [95% CI, 0.65-0.93] to 0.85 [95% CI, 0.74-0.96]), higher for OST than FRAX (range, 0.72 [95% CI, 0.68-0.75] to 0.74 [95% CI, 0.60-0.88]), and similar in each of the 4 racial and ethnic groups. Conclusions and Relevance These findings suggest that within each racial and ethnic category, the US FRAX and OST have suboptimal performance in discrimination of MOF in younger postmenopausal women. In contrast, for identifying osteoporosis, OST was excellent. The US version of FRAX should not be routinely used to make screening decisions in younger postmenopausal women. Future investigations should improve existing tools or create new approaches to osteoporosis risk assessment for this age group.